Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration.
Animals
Ciliary Neurotrophic Factor
/ pharmacology
Cytokines
/ metabolism
Disease Models, Animal
Mice, Inbred C57BL
Mice, Transgenic
Photoreceptor Cells, Vertebrate
/ drug effects
Rats
Retina
/ drug effects
Retinal Degeneration
/ genetics
Signal Transduction
/ drug effects
Transcription, Genetic
/ drug effects
Transcriptome
/ drug effects
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
20 04 2020
20 04 2020
Historique:
received:
23
01
2020
accepted:
01
04
2020
entrez:
22
4
2020
pubmed:
22
4
2020
medline:
27
11
2020
Statut:
epublish
Résumé
Ciliary neurotrophic factor (CNTF) has been tested in clinical trials for human retinal degeneration due to its potent neuroprotective effects in various animal models. To decipher CNTF-triggered molecular events in the degenerating retina, we performed high-throughput RNA sequencing analyses using the Rds/Prph2 (P216L) transgenic mouse as a preclinical model for retinitis pigmentosa. In the absence of CNTF treatment, transcriptome alterations were detected at the onset of rod degeneration compared with wild type mice, including reduction of key photoreceptor transcription factors Crx, Nrl, and rod phototransduction genes. Short-term CNTF treatments caused further declines of photoreceptor transcription factors accompanied by marked decreases of both rod- and cone-specific gene expression. In addition, CNTF triggered acute elevation of transcripts in the innate immune system and growth factor signaling. These immune responses were sustained after long-term CNTF exposures that also affected neuronal transmission and metabolism. Comparisons of transcriptomes also uncovered common pathways shared with other retinal degeneration models. Cross referencing bulk RNA-seq with single-cell RNA-seq data revealed the CNTF responsive cell types, including Müller glia, rod and cone photoreceptors, and bipolar cells. Together, these results demonstrate the influence of exogenous CNTF on the retinal transcriptome landscape and illuminate likely CNTF impacts in degenerating human retinas.
Identifiants
pubmed: 32313077
doi: 10.1038/s41598-020-63519-1
pii: 10.1038/s41598-020-63519-1
pmc: PMC7171121
doi:
Substances chimiques
Ciliary Neurotrophic Factor
0
Cytokines
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6593Subventions
Organisme : NEI NIH HHS
ID : P30 EY000331
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY026319
Pays : United States
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